Oct4, a member of the POU-domain transcription factor family, is expressed in pluripotent embryonic stem and germ cells (Okamoto et al., Cell. (1990), 60(3):461-72; Rosner et al., Nature (1990), 345(6277):686-92; and Burdon et al., Trends Cell Biol. (2002), 12(9):432-8). The expression of Oct4 is downregulated during differentiation, suggesting that Oct4 plays a pivotal role in mammalian development (Pesce et al., Mech Dev. 1998; 71(1-2):89-98). SirT1 is necessary for the maintenance of genomic stability, which renders it a potential target for eukaryotic anti-aging research (Oberdoerffer et al., Cell. 2008; 135(5):907-18). The SirT1-related life-extension effect and its neuroprotective capacity have been attributed to its ability to enhance the antioxidative stress response and reduce inflammatory damage (Sedding et al., Biol. Chem. 2008; 389(3):279-83; and Gan et al., Aging Cell. 2010; 9(5):924-9).
Cellular reprogramming has the ability to counteract the mechanisms of cellular aging and bring the cells to a self-renewing, rejuvenescent state (Prigione et al., Stem Cells. 2010; 28(4):721-33; and Li et al., Biomaterials. 2011; 32(26):5994-6005). A low degree of DNA methylation in the promoter region of pluripotency regulators, such as Oct4, is representative of stem cells or reprogramming pluripotent stem cells (Okita et al., Nature. 2007; 448(7151):313-7; and Mikkelsen et al., Nature. 2008; 454(7200):49-55). Self-renewal and pluripotency are important features of embryonic stem cells, and Oct4 plays a key role in the maintenance of these processes (Burdon et al., Trends Cell Biol. 2002; 12(9):432-8; and Boiani et al., Nat Rev Mol Cell Biol. 2005; 6(11):872-84). Endogenous Oct4 expression is essential for maintaining stem-like pluripotency (Boiani et al., Genes Dev. 2002; 16(10):1209-19), and demethylation of the Oct4 promoter has been considered a potent hallmark of the nuclear reprogramming process (Lowry et al., Proc Natl Acad Sci USA. 2008; 105(8):2883-8).